Although anthraquinone derivatives possess significant antitumor activity, most of them also displayed those side effects like cardiotoxicity, mainly owing to their inhibition of topoisomerase II of DNA repair mechanisms. Our raised design strategy by switching therapeutic target from topoisomerase II to histone deacetylase (HDAC) has been applied to the design of anthraquinone derivatives in current study. Consequently, a series of novel HDAC inhibitors with a tricylic diketone of anthraquinone as a cap group have been synthesized. After screening and evaluation, compounds 4b, 4d, 7b and 7d have displayed the comparable inhibition in enzymatic activity and cell proliferation than that of Vorinostat (SAHA). Notably, compound 4b showed certain selectivity of antiproliferative effects on cancer cell lines over non-cancer cell lines.

中文翻译：

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一系列以蒽醌为帽基的新型HDAC抑制剂。

尽管蒽醌衍生物具有显着的抗肿瘤活性，但它们大多数还表现出诸如心脏毒性的副作用，这主要是由于它们抑制了DNA修复机制的拓扑异构酶II。通过将治疗目标从拓扑异构酶II转换为组蛋白脱乙酰基酶（HDAC），我们提出的改进设计策略已应用于当前研究中的蒽醌衍生物设计。因此，合成了一系列以蒽醌的三聚二酮为帽基的新型HDAC抑制剂。经过筛选和评估后，化合物4b，4d，7b和7d对酶活性和细胞增殖的抑制作用与伏立诺他（SAHA）相当。值得注意的是，与非癌细胞系相比，化合物4b对癌细胞系显示出一定的抗增殖作用选择性。